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Rapid Cancer Detection by Topically Spraying a gamma-Glutamyltranspeptidase-Activated Fluorescent Probe

  1. Author:
    Urano, Y.
    Sakabe, M.
    Kosaka, N.
    Ogawa, M.
    Mitsunaga, M.
    Asanuma, D.
    Kamiya, M.
    Young, M. R.
    Nagano, T.
    Choyke, P. L.
    Kobayashi, H.

  2. Author Address

    [Urano, Yasuteru; Asanuma, Daisuke; Kamiya, Mako] Univ Tokyo, Grad Sch Med, Tokyo 1130033, Japan. [Urano, Yasuteru] Japan Sci & Technol Agcy, Basic Res Program, Tokyo 1020075, Japan. [Sakabe, Masayo; Nagano, Tetsuo] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan. [Kosaka, Nobuyuki; Ogawa, Mikako; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Young, Matthew R.] NCI, Lab Can Prevent, Ctr Canc Res, NIH, Frederick, MD 21702 USA.;Urano, Y (reprint author), Univ Tokyo, Grad Sch Med, Tokyo 1130033, Japan;uranokun@m.u-tokyo.ac.jp kobayash@mail.nih.gov
    1. Year: 2011
    2. Date: Nov
  2. Journal: Science Translational Medicine
    1. 3
    2. 110
    3. Pages: 10
  4. Type of Article: Article
  5. ISSN: 1946-6234
  1. Abstract:

    The ability of the unaided human eye to detect small cancer foci or accurate borders between cancer and normal tissue during surgery or endoscopy is limited. Fluorescent probes are useful for enhancing visualization of small tumors but are typically limited by either high background signal or the requirement for administration hours to days before use. We synthesized a rapidly activatable, cancer-selective fluorescence imaging probe, gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), with intramolecular spirocyclic caging for complete quenching. Activation occurs by rapid one-step cleavage of glutamate with gamma-glutamyltranspeptidase (GGT), which is not expressed in normal tissue, but is overexpressed on the cell membrane of various cancer cells, thus leading to complete uncaging and dequenching of the fluorescence probe. In vitro activation of gGlu-HMRG was evident in 11 human ovarian cancer cell lines tested. In vivo in mouse models of disseminated human peritoneal ovarian cancer, activation of gGlu-HMRG occurred within 1 min of topically spraying the tumor, creating high signal contrast between the tumor and the background. The gGlu-HMRG probe is practical for clinical application during surgical or endoscopic procedures because of its rapid and strong activation upon contact with GGT on the surface of cancer cells.

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External Sources

  1. View record in Web of Science®
  2. WOS: 000297407800006

Library Notes

  1. Fiscal Year: FY2011-2012
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